Andrew Sweatt

All Publications

• Computational platform for doctor-artificial intelligence cooperation in pulmonary arterial hypertension prognostication: a pilot study. ERJ open research Kheyfets, V. O., Sweatt, A. J., Gomberg-Maitland, M., Ivy, D. D., Condliffe, R., Kiely, D. G., Lawrie, A., Maron, B. A., Zamanian, R. T., Stenmark, K. R. 2023; 9 (1)

  Abstract

  Pulmonary arterial hypertension (PAH) is a heterogeneous and complex pulmonary vascular disease associated with substantial morbidity. Machine-learning algorithms (used in many PAH risk calculators) can combine established parameters with thousands of circulating biomarkers to optimise PAH prognostication, but these approaches do not offer the clinician insight into what parameters drove the prognosis. The approach proposed in this study diverges from other contemporary phenotyping methods by identifying patient-specific parameters driving clinical risk.We trained a random forest algorithm to predict 4-year survival risk in a cohort of 167 adult PAH patients evaluated at Stanford University, with 20% withheld for (internal) validation. Another cohort of 38 patients from Sheffield University were used as a secondary (external) validation. Shapley values, borrowed from game theory, were computed to rank the input parameters based on their importance to the predicted risk score for the entire trained random forest model (global importance) and for an individual patient (local importance).Between the internal and external validation cohorts, the random forest model predicted 4-year risk of death/transplant with sensitivity and specificity of 71.0-100% and 81.0-89.0%, respectively. The model reinforced the importance of established prognostic markers, but also identified novel inflammatory biomarkers that predict risk in some PAH patients.These results stress the need for advancing individualised phenotyping strategies that integrate clinical and biochemical data with outcome. The computational platform presented in this study offers a critical step towards personalised medicine in which a clinician can interpret an algorithm's assessment of an individual patient.

  View details for DOI 10.1183/23120541.00484-2022

  View details for PubMedID 36776484

  View details for PubMedCentralID PMC9907150

• Pulmonary Vasodilator Response of Combined Inhaled Epoprostenol and Inhaled Milrinone in Cardiac Surgical Patients. Anesthesia and analgesia Elmi-Sarabi, M., Jarry, S., Couture, E. J., Haddad, F., Cogan, J., Sweatt, A. J., Rousseau-Saine, N., Beaubien-Souligny, W., Fortier, A., Denault, A. Y. 2022

  Abstract

  BACKGROUND: Pulmonary hypertension (PH) and right ventricular (RV) dysfunction are major complications in cardiac surgery. Intraoperative management of patients at high risk of RV failure should aim to reduce RV afterload and optimize RV filling pressures, while avoiding systemic hypotension, to facilitate weaning from cardiopulmonary bypass (CPB). Inhaled epoprostenol and inhaled milrinone (iE&iM) administered in combination before CPB may represent an effective strategy to facilitate separation from CPB and reduce requirements for intravenous inotropes during cardiac surgery. Our primary objective was to report the rate of positive pulmonary vasodilator response to iE&iM and, second, how it relates to perioperative outcomes in cardiac surgery.METHODS: This is a retrospective cohort study of consecutive patients with PH or RV dysfunction undergoing on-pump cardiac surgery at the Montreal Heart Institute from July 2013 to December 2018 (n = 128). iE&iM treatment was administered using an ultrasonic mesh nebulizer before the initiation of CPB. Demographic and baseline clinical data, as well as hemodynamic, intraoperative, and echocardiographic data, were collected using electronic records. An increase of 20% in the mean arterial pressure (MAP) to mean pulmonary artery pressure (MPAP) ratio was used to indicate a positive response to iE&iM.RESULTS: In this cohort, 77.3% of patients were responders to iE&iM treatment. Baseline systolic pulmonary artery pressure (SPAP) (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.24-2.16 per 5 mm Hg; P = .0006) was found to be a predictor of pulmonary vasodilator response, while a European System for Cardiac Operative Risk Evaluation (EuroSCORE II) score >6.5% was a predictor of nonresponse to treatment (≤6.5% vs >6.5% [reference]: OR, 5.19; 95% CI, 1.84-14.66; P = .002). Severity of PH was associated with a positive response to treatment, where a higher proportion of responders had MPAP values >30 mm Hg (42.4% responders vs 24.1% nonresponders; P = .0237) and SPAP values >55 mm Hg (17.2% vs 3.4%; P = .0037). Easier separation from CPB was also associated with response to iE&iM treatment (69.7% vs 58.6%; P = .0181). A higher proportion of nonresponders had a very difficult separation from CPB and required intravenous inotropic drug support compared to responders, for whom easy separation from CPB was more frequent. Use of intravenous inotropes after CPB was lower in responders to treatment (8.1% vs 27.6%; P = .0052).CONCLUSIONS: A positive pulmonary vasodilator response to treatment with a combination of iE&iM before initiation of CPB was observed in 77% of patients. Higher baseline SPAP was an independent predictor of pulmonary vasodilator response, while EuroSCORE II >6.5% was a predictor of nonresponse to treatment.

  View details for DOI 10.1213/ANE.0000000000006192

  View details for PubMedID 36121254

• Endogenous Retroviral Elements Generate Pathologic Neutrophils in Pulmonary Arterial Hypertension. American journal of respiratory and critical care medicine Taylor, S., Isobe, S., Cao, A., Contrepois, K., Benayoun, B. A., Jiang, L., Wang, L., Melemenidis, S., Ozen, M. O., Otsuki, S., Shinohara, T., Sweatt, A. J., Kaplan, J., Moonen, J., Marciano, D. P., Gu, M., Miyagawa, K., Hayes, B., Sierra, R. G., Kupitz, C. J., Del Rosario, P. A., Hsi, A., Thompson, A. A., Ariza, M. E., Demirci, U., Zamanian, R. T., Haddad, F., Nicolls, M. R., Snyder, M. P., Rabinovitch, M. 2022

  Abstract

  RATIONALE: The role of neutrophils and their extracellular vesicles (EVs) in the pathogenesis of pulmonary arterial hypertension is unclear.OBJECTIVES: Relate functional abnormalities in pulmonary arterial hypertension neutrophils and their EVs to mechanisms uncovered by proteomic and transcriptomic profiling.METHODS: Production of elastase, release of extracellular traps, adhesion and migration were assessed in neutrophils from pulmonary arterial hypertension patients and control subjects. Proteomic analyses were applied to explain functional perturbations, and transcriptomic data were used to find underlying mechanisms. CD66b-specific neutrophil EVs were isolated from plasma of patients with pulmonary arterial hypertension and we determined whether they produce pulmonary hypertension in mice.MEASUREMENTS AND MAIN RESULTS: Neutrophils from pulmonary arterial hypertension patients produce and release increased neutrophil elastase, associated with enhanced extracellular traps. They exhibit reduced migration and increased adhesion attributed to elevated beta1integrin and vinculin identified on proteomic analysis and previously linked to an antiviral response. This was substantiated by a transcriptomic interferon signature that we related to an increase in human endogenous retrovirus k envelope protein. Transfection of human endogenous retrovirus k envelope in a neutrophil cell line (HL-60) increases neutrophil elastase and interferon genes, whereas vinculin is increased by human endogenous retrovirus k dUTPase that is elevated in patient plasma. Neutrophil EVs from patient plasma contain increased neutrophil elastase and human endogenous retrovirus k envelope and induce pulmonary hypertension in mice, mitigated by elafin, an elastase inhibitor.CONCLUSIONS: Elevated human endogenous retroviral elements and elastase link a neutrophil innate immune response to pulmonary arterial hypertension.

  View details for DOI 10.1164/rccm.202102-0446OC

  View details for PubMedID 35696338

• Peripheral Blood Inflammation Profile of Patients with Pulmonary Arterial Hypertension Using the High-Throughput Olink Proteomics Platform AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY Mickael, C., Kheyfets, V. O., Langouet-Astrie, C., Lee, M. H., Sanders, L. A., Trentin, C. O., Sweatt, A. J., Zamanian, R. T., Bull, T. M., Stenmark, K., Graham, B. B., Tuder, R. M. 2022; 66 (5): 581-583

  View details for Web of Science ID 000790563500016

• Peripheral Blood Inflammation Profile of Patients with Pulmonary Arterial Hypertension Using the High-Throughput Olink Proteomics Platform. American journal of respiratory cell and molecular biology Mickael, C., Kheyfets, V. O., Langouet-Astrie, C., Lee, M. H., Sanders, L. A., Trentin, C. O., Sweatt, A. J., Zamanian, R. T., Bull, T. M., Stenmark, K., Graham, B. B., Tuder, R. M. 2022; 66 (5): 580-581

  View details for DOI 10.1165/rcmb.2021-0369LE

  View details for PubMedID 35486078

• Harnessing Big Data to Advance Treatment and Understanding of Pulmonary Hypertension CIRCULATION RESEARCH Rhodes, C. J., Sweatt, A. J., Maron, B. A. 2022; 130 (9): 1423-1444

  Abstract

  Pulmonary hypertension is a complex disease with multiple causes, corresponding to phenotypic heterogeneity and variable therapeutic responses. Advancing understanding of pulmonary hypertension pathogenesis is likely to hinge on integrated methods that leverage data from health records, imaging, novel molecular -omics profiling, and other modalities. In this review, we summarize key data sets generated thus far in the field and describe analytical methods that hold promise for deciphering the molecular mechanisms that underpin pulmonary vascular remodeling, including machine learning, network medicine, and functional genetics. We also detail how genetic and subphenotyping approaches enable earlier diagnosis, refined prognostication, and optimized treatment prediction. We propose strategies that identify functionally important molecular pathways, bolstered by findings across multi-omics platforms, which are well-positioned to individualize drug therapy selection and advance precision medicine in this highly morbid disease.

  View details for DOI 10.1161/CIRCRESAHA.121.319969

  View details for Web of Science ID 000787318200017

  View details for PubMedID 35482840

  View details for PubMedCentralID PMC9070103

• Exploring disease interrelationships in patients with lymphatic disorders: A single center retrospective experience. Clinical and translational medicine Rockson, S. G., Zhou, X., Zhao, L., Hosseini, D. K., Jiang, X., Sweatt, A. J., Kim, D., Tian, W., Snyder, M. P., Nicolls, M. R. 2022; 12 (4): e760

  Abstract

  The lymphatic contribution to the circulation is of paramount importance in regulating fluid homeostasis, immune cell trafficking/activation and lipid metabolism. In comparison to the blood vasculature, the impact of the lymphatics has been underappreciated, both in health and disease, likely due to a less well-delineated anatomy and function. Emerging data suggest that lymphatic dysfunction can be pivotal in the initiation and development of a variety of diseases across broad organ systems. Understanding the clinical associations between lymphatic dysfunction and non-lymphatic morbidity provides valuable evidence for future investigations and may foster the discovery of novel biomarkers and therapies.We retrospectively analysed the electronic medical records of 724 patients referred to the Stanford Center for Lymphatic and Venous Disorders. Patients with an established lymphatic diagnosis were assigned to groups of secondary lymphoedema, lipoedema or primary lymphovascular disease. Individuals found to have no lymphatic disorder were served as the non-lymphatic controls. The prevalence of comorbid conditions was enumerated. Pairwise co-occurrence pattern analyses, validated by Jaccard similarity tests, was utilised to investigate disease-disease interrelationships.Comorbidity analyses underscored the expected relationship between the presence of secondary lymphoedema and those diseases that damage the lymphatics. Cardiovascular conditions were common in all lymphatic subgroups. Additionally, statistically significant alteration of disease-disease interrelationships was noted in all three lymphatic categories when compared to the control population.The presence or absence of a lymphatic disease significantly influences disease interrelationships in the study cohorts. As a physiologic substrate, the lymphatic circulation may be an underappreciated participant in disease pathogenesis. These relationships warrant further, prospective scrutiny and study.

  View details for DOI 10.1002/ctm2.760

  View details for PubMedID 35452183

• What's new in pulmonary hypertension clinical research: lessons from the best abstracts at the 2020 American Thoracic Society International Conference. Pulmonary circulation Sweatt, A. J., Reddy, R., Rahaghi, F. N., Al-Naamani, N., American Thoracic Society Pulmonary Circulation Assembly Early Career Working Group 2021; 11 (3): 20458940211040713

  Abstract

  In this conference paper, we review the 2020 American Thoracic Society International Conference session titled, "What's New in Pulmonary Hypertension Clinical Research: Lessons from the Best Abstracts". This virtual mini-symposium took place on 21 October 2020, in lieu of the annual in-person ATS International Conference which was cancelled due to the COVID-19 pandemic. Seven clinical research abstracts were selected for presentation in the session, which encompassed five major themes: (1) standardizing diagnosis and management of pulmonary hypertension, (2) improving risk assessment in pulmonary arterial hypertension, (3) evaluating biomarkers of disease activity, (4) understanding metabolic dysregulation across the spectrum of pulmonary hypertension, and (5) advancing knowledge in chronic thromboembolic pulmonary hypertension. Focusing on these five thematic contexts, we review the current state of knowledge, summarize presented research abstracts, appraise their significance and limitations, and then discuss relevant future directions in pulmonary hypertension clinical research.

  View details for DOI 10.1177/20458940211040713

  View details for PubMedID 34471517

• Reply to: Multiple Manifestations of Systemic Sclerosis Affect Walk Distance. American journal of respiratory and critical care medicine Zamanian, R. T., Pinckney, A., Domsic, R. T., Medsger, T., Keyes-Elstein, L., Sweatt, A. J., Welch, B., Goldmuntz, E., Nicolls, M. R., Chung, L., NIH ASC01 Study Group 2021

  View details for DOI 10.1164/rccm.202104-1023LE

  View details for PubMedID 34107229

• NHLBI-CMREF Workshop Report on Pulmonary Vascular DiseaseClassification: JACC State-of-the-Art Review. Journal of the American College of Cardiology Oldham, W. M., Hemnes, A. R., Aldred, M. A., Barnard, J., Brittain, E. L., Chan, S. Y., Cheng, F., Cho, M. H., Desai, A. A., Garcia, J. G., Geraci, M. W., Ghiassian, S. D., Hall, K. T., Horn, E. M., Jain, M., Kelly, R. S., Leopold, J. A., Lindstrom, S., Modena, B. D., Nichols, W. C., Rhodes, C. J., Sun, W., Sweatt, A. J., Vanderpool, R. R., Wilkins, M. R., Wilmot, B., Zamanian, R. T., Fessel, J. P., Aggarwal, N. R., Loscalzo, J., Xiao, L. 2021; 77 (16): 2040–52

  Abstract

  The National Heart, Lung, and Blood Institute and the Cardiovascular Medical Research and Education Fund held a workshop on the application of pulmonary vascular disease omics data to the understanding, prevention, and treatment of pulmonary vascular disease. Experts in pulmonary vascular disease, omics, and data analytics met to identify knowledge gaps and formulate ideas for future research priorities in pulmonary vascular disease in line with National Heart, Lung, and Blood Institute Strategic Vision goals. The group identified opportunities to develop analytic approaches to multiomic datasets, to identify molecular pathways in pulmonary vascular disease pathobiology, and to link novel phenotypes to meaningful clinical outcomes. The committee suggested support for interdisciplinary research teams to develop and validate analytic methods, a national effort to coordinate biosamples and data, a consortium of preclinical investigators to expedite target evaluation and drug development, longitudinal assessment of molecular biomarkers in clinical trials, and a task force to develop a master clinical trials protocol for pulmonary vascular disease.

  View details for DOI 10.1016/j.jacc.2021.02.056

  View details for PubMedID 33888254

• Safety and Efficacy of B-Cell Depletion with Rituximab for the Treatment of Systemic Sclerosis Associated Pulmonary Arterial Hypertension: A Multi-center, Double-blind, Randomized, Placebo-controlled Trial. American journal of respiratory and critical care medicine Zamanian, R. T., Badesch, D., Chung, L., Domsic, R. T., Medsger, T., Pinckney, A., Keyes-Elstein, L., D'Aveta, C., Spychala, M., White, R. J., Hassoun, P. M., Torres, F., Sweatt, A. J., Molitor, J. A., Khanna, D., Maecker, H., Welch, B., Goldmuntz, E., Nicolls, M. R., NIH ASC01 Study Group 2021

  Abstract

  RATIONALE: Systemic sclerosis-pulmonary arterial hypertension (SSc-PAH) is one of the most prevalent and deadly forms of PAH. B cells may contribute to SSc pathogenesis.OBJECTIVE: We investigated the safety and efficacy of B-cell depletion for SSc-PAH.METHODS AND MEASUREMENTS: In an NIH-sponsored, multi-center, double-blinded, randomized, placebo-controlled, proof-of-concept trial, 57 SSc-PAH patients on stable-dose standard medical therapy received two infusions of 1000 mg of rituximab or placebo administered two weeks apart. The primary outcome measure was the change in six-minute walk distance (6MWD) at 24 weeks. Secondary endpoints included safety and invasive hemodynamics. We applied a machine learning approach to predict drug-responsiveness.MAIN RESULTS: We randomized 57 subjects from 2010-2018. In the primary analysis, using data through week 24, the adjusted mean change in 6MWD at 24 weeks favored the treatment arm but did not reach statistical significance (23.6±11.1m vs. 0.5±9.7m, p=0.12). While a negative study, when data through week 48 were also considered, the estimated change in 6MWD at week 24 was 25.5±8.8m for rituximab and 0.4±7.4m for placebo (p=0.03). Rituximab treatment appeared to be safe and well tolerated. Low levels of rheumatoid factor (RF), IL-12, and IL-17 were sensitive and specific as favorable predictors of a rituximab response as measured by an improved 6MWD (ROC AUC 0.88-0.95).CONCLUSIONS: B cell depletion therapy is a potentially effective and safe adjuvant treatment for SSc-PAH. Future studies in these patients can confirm whether the identified biomarkers predict rituximab-responsiveness. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT01086540.

  View details for DOI 10.1164/rccm.202009-3481OC

  View details for PubMedID 33651671

• The Right Heart Network and Risk Stratification in Pulmonary Arterial Hypertension. Chest Haddad, F., Contrepois, K., Amsallem, M., Denault, A. Y., Bernardo, R. J., Jha, A., Taylor, S., Arthur Ataam, J., Mercier, O., Kouznetsova, T., Vonk Noordegraaf, A., Zamanian, R. T., Sweatt, A. J. 2021

  Abstract

  Prognosis in pulmonary arterial hypertension (PAH) is closely related to indexes of right ventricular function. A better understanding of their relationship may provide important implications for risk stratification in PAH.Can clinical network graphs inform risk stratification in PAH?The study cohort consisted of 231 patients with PAH followed up for a median of 7.1 years. An undirected, correlation network was used to visualize the relationship between clinical features in PAH. This network was enriched for right heart parameters and included N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP), comprehensive echocardiographic parameters, and hemodynamics, as well as 6-min walk distance (6MWD), vital signs, laboratory data, and diffusing capacity for carbon monoxide (Dlco). Connectivity was assessed by using eigenvector and betweenness centrality to reflect global and regional connectivity, respectively. Cox proportional hazards regression was used to model event-free survival for the combined end point of death or lung transplantation.A network of closely intertwined features centered around NT-proBNP with 6MWD emerging as a secondary hub were identified. Less connected nodes included Dlco, systolic BP, albumin, and sodium. Over the follow-up period, death or transplantation occurred in 92 patients (39.8%). A strong prognostic model was achieved with a Harrell's C-index of 0.81 (0.77-0.85) when combining central right heart features (NT-proBNP and right ventricular end-systolic remodeling index) with 6MWD and less connected nodes (Dlco, systolic BP, albumin, sodium, sex, connective tissue disease etiology, and prostanoid therapy). When added to the baseline risk model, serial change in NT-proBNP significantly improved outcome prediction at 5 years (increase in C-statistic of 0.071 ± 0.024; P = .003).NT-proBNP emerged as a central hub in the intertwined PAH network. Connectivity analysis provides explainability for feature selection and combination in outcome models.

  View details for DOI 10.1016/j.chest.2021.10.045

  View details for PubMedID 34774527

• Severe Pulmonary Arterial Hypertension is Characterized by Increased Neutrophil Elastase and Relative Elafin Deficiency. Chest Sweatt, A. J., Miyagawa, K., Rhodes, C. J., Taylor, S., Del Rosario, P. A., Hsi, A., Haddad, F., Spiekerkoetter, E., Bental-Roof, M., Bland, R. D., Swietlik, E. M., Gräf, S., Wilkins, M. R., Morrell, N. W., Nicolls, M. R., Rabinovitch, M., Zamanian, R. T. 2021

  Abstract

  Preclinical evidence implicates neutrophil elastase (NE) in PAH pathogenesis, and the NE inhibitor elafin is under early therapeutic investigation.Are circulating NE and elafin levels abnormal in PAH and associated with clinical severity?. In an observational Stanford University PAH cohort (N=249), plasma NE and elafin were measured in comparison to healthy controls (N=106) then related to clinical features and relevant ancillary biomarkers. Cox regression models were fitted with cubic spline functions to associate NE and elafin with survival. To validate prognostic relationships, we analyzed two United Kingdom cohorts (N=75, N=357). Mixed effects models evaluated NE and elafin changes during disease progression. Finally, we studied effects of NE/elafin balance on pulmonary artery endothelial cells (PAECs) from PAH patients.Relative to controls, patients had increased NE (205.1 [123.6-387.3] vs. 97.6 [74.4-126.6] ng/mL, P<0.0001) and decreased elafin (32.0 [15.3-59.1] vs. 45.5 [28.1-92.8] ng/mL, P<0.0001) independent of PAH subtype, illness duration, and therapies. Higher NE associated with worse symptom severity, shorter six-minute walk distance, higher NT-proBNP, greater right ventricular dysfunction, worse hemodynamics, increased circulating neutrophils, elevated cytokine levels, and lower blood BMPR2 expression. In Stanford patients, NE>168.5 ng/mL portended increased mortality risk after adjustment for known clinical predictors (HR 2.52, CI 1.36-4.65, P=0.003) or prognostic cytokines (HR 2.63, CI 1.42-4.87, P=0.001), and NE added incremental value to established PAH risk scores. Similar prognostic thresholds were identified in validation cohorts. Longitudinal NE changes tracked with clinical trends and outcomes. PAH-PAECs exhibited increased apoptosis and attenuated angiogenesis when exposed to NE at the level observed in patients' blood. Elafin rescued PAEC homeostasis, yet the required dose exceeded levels found in patients.NE is increased and elafin deficient across PAH subtypes. NE associates with disease severity and outcomes, and this target-specific biomarker could facilitate therapeutic development of elafin.

  View details for DOI 10.1016/j.chest.2021.06.028

  View details for PubMedID 34181952

• Prescription Patterns for Pulmonary Vasodilators in the Treatment of Pulmonary Hypertension Associated With Chronic Lung Diseases: Insights From a Clinician Survey. Frontiers in medicine Thomas, C. A., Lee, J., Bernardo, R. J., Anderson, R. J., Glinskii, V., Sung, Y. K., Kudelko, K., Hedlin, H., Sweatt, A., Kawut, S. M., Raj, R., Zamanian, R. T., de Jesus Perez, V. 1800; 8: 764815

  Abstract

  Background: Pulmonary hypertension is a complication of chronic lung diseases (PH-CLD) associated with significant morbidity and mortality. Management guidelines for PH-CLD emphasize the treatment of the underlying lung disease, but the role of PH-targeted therapy remains controversial. We hypothesized that treatment approaches for PH-CLD would be variable across physicians depending on the type of CLD and the severity of PH. Methods and Results: Between May and July 2020, we conducted an online survey of PH experts asking for their preferred treatment approach in seven hypothetical cases of PH-CLD of varying severity. We assessed agreement amongst clinicians for initial therapy choice using Fleiss' kappa calculations. Over 90% of respondents agreed that they would treat cases of severe PH in the context of mild lung disease with some form of PH-targeted therapy. For cases of severe PH in the context of severe lung disease, over 70% of respondents agreed to use PH-targeted therapy. For mild PH and mild lung disease cases, <50% of respondents chose to start PH-specific therapy. There was overall poor agreement between respondents in the choice to use mono-, double or triple combination therapy with PH-specific agents in all cases. Conclusion: Although management guidelines discourage the routine use of PH-targeted therapies to treat PH-CLD patients, most physicians choose to treat patients with some form of PH-targeted therapy. The choice of therapy and treatment approach are variable and appear to be influenced by the severity of the PH and the underlying lung disease.

  View details for DOI 10.3389/fmed.2021.764815

  View details for PubMedID 34926507

• Quantifying the Influence of Wedge Pressure, Age, and Heart Rate on the Systolic Thresholds for Detection of Pulmonary Hypertension. Journal of the American Heart Association Amsallem, M., Tedford, R. J., Denault, A., Sweatt, A. J., Guihaire, J., Hedman, K., Peighambari, S., Kim, J. B., Li, X., Miller, R. J., Mercier, O., Fadel, E., Zamanian, R., Haddad, F. 2020: e016265

  Abstract

  Background The strong linear relation between mean (MPAP) and systolic (SPAP) pulmonary arterial pressure (eg, SPAP=1.62*MPAP) has been mainly reported in precapillary pulmonary hypertension. This study sought to quantify the influence of pulmonary arterial wedge pressure (PAWP), heart rate, and age on the MPAP-SPAP relation. Methods and Results An allometric equation relating invasive MPAP and SPAP was developed in 1135 patients with pulmonary arterial hypertension, advanced lung disease, chronic thromboembolic pulmonary hypertension, or left heart failure. The equation was validated in 60885 patients from the United Network for Organ Sharing (UNOS) database referred for heart and/or lung transplant. The MPAP/SPAP longitudinal stability was assessed in pulmonary arterial hypertension with repeated right heart catheterization. The equation obtained was SPAP=1.39*MPAP*PAWP-0.07*(60/heart rate)0.12*age0.08 (P<0.001). It was validated in the UNOS cohort (R2=0.93, P<0.001), regardless of the type of organ(s) patients were listed for (mean bias [-1.96SD; 1.96SD] was 0.94 [-8.00; 9.88] for heart, 1.34 [-7.81; 10.49] for lung and 0.25 [-16.74; 17.24] mmHg for heart-lung recipients). Thresholds of SPAP for MPAP=25 and 20mmHg were lower in patients with higher PAWP (37.2 and 29.8mmHg) than in those with pulmonary arterial hypertension (40.1 and 32.0mmHg). In 186 patients with pulmonary arterial hypertension, the predicted MPAP/SPAP was stable over time (0.63±0.03 at baseline and follow-up catheterization, P=0.43). Conclusions This study quantifies the impact of PAWP, and to a lesser extent heart rate and age, on the MPAP-SPAP relation, supporting lower SPAP thresholds for pulmonary hypertension diagnosis in patients with higher PAWP for echocardiography-based epidemiological studies.

  View details for DOI 10.1161/JAHA.119.016265

  View details for PubMedID 32419583

• PROGNOSTIC VALUE OF THE RELATIVE PULMONARY PRESSURE RATIO AND ITS TRAJECTORY IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION Bagherzadeh, S. P., Amsallem, M., Denault, A., Sweatt, A., Kudelko, K., Sung, Y., Haddad, F., Zamanian, R. ELSEVIER SCIENCE INC. 2020: 2096

  View details for Web of Science ID 000522979102081

• Targeted Proteomics of Right Heart Adaptation to Pulmonary Arterial Hypertension. The European respiratory journal Amsallem, M. n., Sweatt, A. J., Arthur Ataam, J. n., Guihaire, J. n., Lecerf, F. n., Lambert, M. n., Ghigna, M. R., Ali, M. K., Mao, Y. n., Fadel, E. n., Rabinovitch, M. n., de Jesus Perez, V. n., Spiekerkoetter, E. n., Mercier, O. n., Haddad, F. n., Zamanian, R. T. 2020

  Abstract

  No prior proteomic screening study has centered on the right ventricle (RV) in pulmonary arterial hypertension (PAH). This study investigates the circulating proteomic profile associated with right heart maladaptive phenotype (RHMP) in PAH.Plasma proteomic profiling was performed using multiplex immunoassay in 121 PAH patients (discovery cohort) and 76 patients (validation cohort). The association between proteomic markers and RHMP (defined by the Mayo right heart score [combining RV strain, New York Heart Association NYHA class and NT-proBNP] and Stanford score [RV end-systolic remodelling index, NYHA and NT-proBNP]) was assessed by partial least squares regression. Biomarkers expressions were measured in RV samples from PAH patients and controls, and pulmonary artery banding (PAB) mice.High levels of hepatic growth factor (HGF), stem cell growth factor beta, nerve growth factor and stromal derived factor-1 were associated with worse Mayo and Stanford scores independently from pulmonary resistance or pressure in both cohorts (the validation cohort had more severe disease features: lower cardiac index and higher NT-proBNP). In both cohorts, HGF added value to the REVEAL score in the prediction of death, transplant, or hospitalisation at 3 years. RV expression levels of HGF and its receptor c-Met were higher in end-stage PAH patients than controls, and in PAB mice than shams.High plasma HGF levels are associated with RHMP and predictive of 3-year clinical worsening. Both HGF and c-Met RV expression levels are increased in PAH. Assessing plasma HGF levels might identify patients at risk for heart failure who warrant closer follow-up and intensified therapy.

  View details for DOI 10.1183/13993003.02428-2020

  View details for PubMedID 33334941

• Mural Cell SDF1 Signaling is Associated with the Pathogenesis of Pulmonary Arterial Hypertension. American journal of respiratory cell and molecular biology Yuan, K. n., Liu, Y. n., Zhang, Y. n., Nathan, A. n., Tian, W. n., Yu, J. n., Sweatt, A. J., Condon, D. n., Chakraborty, A. n., Agarwal, S. n., Auer, N. n., Zhang, S. n., Wu, J. C., Zamanian, R. T., Nicolls, M. R., de Jesus Perez, V. A. 2020

  Abstract

  Pulmonary artery smooth muscle cells (PASMCs) and pericytes are NG2+ mural cells that provide structural support to pulmonary arteries and capillaries. In pulmonary arterial hypertension (PAH), both mural cell types contribute to PA muscularization but whether similar mechanisms are responsible for their behavior is unknown.RNA-Seq was used to compare the gene profile of pericytes and PASMCs from PAH and healthy lungs. NG2-Cre-ER mice were used to generate NG2-selective reporter mice (NG2tdT) for cell lineage identification and tamoxifen-inducible mice for NG2-selective SDF1 knockout (SDF1NG2-KO).Hierarchical clustering of RNA-seq data demonstrated that the genetic profile of PAH pericytes and PASMCs is highly similar. Cellular lineage staining studies on NG2tdT mice in chronic hypoxia showed that similar to PAH, tdT+ cells accumulate in muscularized microvessels and demonstrate significant upregulation of SDF1, a chemokine involved in chemotaxis and angiogenesis. Compared to controls, SDF1NG2-KO mice in chronic hypoxia had reduced muscularization and lower abundance of NG2+ cells around microvessels. SDF1 stimulation in healthy pericytes induced greater contractility and impaired their capacity to establish endothelial-pericyte communications. In contrast, SDF1 knockdown reduced PAH pericyte contractility and improved their capacity to associate with vascular tubes in co-culture.SDF1 is upregulated in NG2+ mural cells and is associated with PA muscularization. Targeting SDF1 could help prevent and/or reverse muscularization in PAH.

  View details for DOI 10.1165/rcmb.2019-0401OC

  View details for PubMedID 32084325

• Genetic Admixture and Survival in Diverse Populations with Pulmonary Arterial Hypertension. American journal of respiratory and critical care medicine Karnes, J. H., Wiener, H. W., Schwantes-An, T. H., Natarajan, B. n., Sweatt, A. J., Chaturvedi, A. n., Arora, A. n., Batai, K. n., Nair, V. n., Steiner, H. E., Giles, J. B., Yu, J. n., Hosseini, M. n., Pauciulo, M. W., Lutz, K. A., Coleman, A. W., Feldman, J. n., Vanderpool, R. n., Tang, H. n., Garcia, J. G., Yuan, J. X., Kittles, R. n., de Jesus Perez, V. n., Zamanian, R. T., Rischard, F. n., Tiwari, H. K., Nichols, W. C., Benza, R. L., Desai, A. A. 2020

  Abstract

  Limited information is available on racial/ethnic differences in pulmonary arterial hypertension (PAH).Determine effects of race/ethnicity and ancestry on mortality and disease outcomes in diverse patients with PAH.Group 1 PAH patients were included from two national registries with genome-wide data and two local cohorts and further incorporated in a global meta-analysis. Hazard ratios (HRs) were calculated for transplant-free all-cause mortality in Hispanics with Non-Hispanic whites (NHWs) as the reference group. Odds ratios (ORs) for inpatient-specific mortality in PAH patients were also calculated for race/ethnic groups from an additional National Inpatient Sample (NIS) dataset, not included in the meta-analysis.After covariate adjustment, self-reported Hispanics (n=290) exhibited significantly reduced mortality versus NHWs (n=1970) after global meta-analysis (HR 0.60[0.41-0.87], p=0.008). Although not significant, increasing Native American genetic ancestry appeared to account for part of the observed mortality benefit (HR 0.48[0.23-1.01], p=0.053) in the two national registries. Finally, in the NIS, an inpatient mortality benefit was also observed for Hispanics (n=1524) versus NHWs (n=8829; OR 0.65[0.50-0.84], p=0.001). An inpatient mortality benefit was observed for Native Americans (n=185; OR 0.38[0.15-0.93], p=0.034).This study demonstrates a reproducible survival benefit for Hispanic Group 1 PAH patients in multiple clinical settings. Our results implicate contributions of genetic ancestry to differential survival in PAH.

  View details for DOI 10.1164/rccm.201907-1447OC

  View details for PubMedID 31916850

• Hemodynamic trajectories and outcomes in patients with pulmonary arterial hypertension. Pulmonary circulation Amsallem, M. n., Bagherzadeh, S. P., Boulate, D. n., Sweatt, A. J., Kudelko, K. T., Sung, Y. K., Feinstein, J. A., Fadel, E. n., Mercier, O. n., Denault, A. n., Haddad, F. n., Zamanian, R. n. 2020; 10 (4): 2045894020941343

  Abstract

  The relative pulmonary to systemic pressure ratio (mean pulmonary arterial pressure/mean arterial pressure) has been proven to be valuable in cardiac surgery. Little is known on the prognostic value of baseline and trajectory of mean pulmonary arterial pressure/mean arterial pressure in pulmonary arterial hypertension. Patients with confirmed idiopathic, familial, drug and toxins, or connective tissue disease-related pulmonary arterial hypertension and at least one complete right heart catheterization were included and prospectively followed-up for 5.9 ± 4.03 years. Correlates of the primary end point (i.e. death or lung transplant need) during follow-up were determined using Cox regression modeling. Results showed that among the 308 patients included, 187 had at least one follow-up catheterization (median time between catheterizations: 2.16 (1.16-3.19) years). In the total cohort (mean age 47.3 ± 14.9 years, 82.8% of female and 58.1% in New York Heart Association class 3 or 4), mean pulmonary arterial pressure/mean arterial pressure (1.38 (1.07-1.77)) was associated with outcome (p = 0.01). Mean pulmonary arterial pressure/mean arterial pressure was incremental to a basic model (including right atrial pressure, systolic blood pressure, New York Heart Association class 3 or 4, and connective tissue disease) for outcome prediction, while mean pulmonary arterial pressure was not. In the 187 patients with a follow-up catheterization, both delta mean pulmonary arterial pressure and delta mean pulmonary arterial pressure/mean arterial pressure were associated with outcome (1.32 (1.11-1.58) and 1.31 (1.1-1.57) respectively, p < 0.01). Mean pulmonary arterial pressure and mean pulmonary arterial pressure/mean arterial pressure were both incremental to the basic model, while worsening in mean pulmonary arterial pressure or mean pulmonary arterial pressure/mean arterial pressure did not reach significance. In conclusion, mean pulmonary arterial pressure/mean arterial pressure at baseline prognosticates long-term outcome with a significant, albeit modest, incremental value to basic variables.

  View details for DOI 10.1177/2045894020941343

  View details for PubMedID 33335708

  View details for PubMedCentralID PMC7724418

• Survival implications of pulmonary hypertension in end-stage COPD Kapasi, A., Halloran, K., Hirji, A., Lien, D., Mooney, J., Raj, R., Sweatt, A., Weinkauf, J., Zamanian, R. EUROPEAN RESPIRATORY SOC JOURNALS LTD. 2019

  View details for DOI 10.1183/13993003.congress-2019.PA1426

  View details for Web of Science ID 000507372401438

• Elevated pulmonary vascular resistance is associated with increased risk of death in IPF Kapasi, A., Halloran, K., Hirji, A., Lien, D., Mooney, J., Raj, R., Sweatt, A., Weinkauf, J., Zamanian, R. EUROPEAN RESPIRATORY SOC JOURNALS LTD. 2019

  View details for DOI 10.1183/13993003.congress-2019.PA1428

  View details for Web of Science ID 000507372401440

• Discovery of Distinct Immune Phenotypes Using Machine Learning in Pulmonary Arterial Hypertension CIRCULATION RESEARCH Sweatt, A. J., Hedlin, H. K., Balasubramanian, V., Hsi, A., Blum, L. K., Robinson, W. H., Haddad, F., Hickey, P. M., Condliffe, R., Lawrie, A., Nicolls, M. R., Rabinovitch, M., Khatri, P., Zamanian, R. T. 2019; 124 (6): 904–19

  View details for DOI 10.1161/CIRCRESAHA.118.313911

  View details for Web of Science ID 000469341600015

• Discovery of Distinct Immune Phenotypes Using Machine Learning in Pulmonary Arterial Hypertension. Circulation research Sweatt, A. J., Hedlin, H. K., Balasubramanian, V. n., Hsi, A. n., Blum, L. K., Robinson, W. H., Haddad, F. n., Hickey, P. M., Condliffe, R. A., Lawrie, A. n., Nicolls, M. R., Rabinovitch, M. n., Khatri, P. n., Zamanian, R. T. 2019

  Abstract

  Accumulating evidence implicates inflammation in pulmonary arterial hypertension (PAH) and therapies targeting immunity are under investigation, though it remains unknown if distinct immune phenotypes exist.Identify PAH immune phenotypes based on unsupervised analysis of blood proteomic profiles.In a prospective observational study of Group 1 PAH patients evaluated at Stanford University (discovery cohort, n=281) and University of Sheffield (validation cohort, n=104) between 2008-2014, we measured a circulating proteomic panel of 48 cytokines, chemokines, and factors using multiplex immunoassay. Unsupervised machine learning (consensus clustering) was applied in both cohorts independently to classify patients into proteomic immune clusters, without guidance from clinical features. To identify central proteins in each cluster, we performed partial correlation network analysis. Clinical characteristics and outcomes were subsequently compared across clusters. Four PAH clusters with distinct proteomic immune profiles were identified in the discovery cohort. Cluster 2 (n=109) had low cytokine levels similar to controls. Other clusters had unique sets of upregulated proteins central to immune networks- cluster 1 (n=58)(TRAIL, CCL5, CCL7, CCL4, MIF), cluster 3 (n=77)(IL-12, IL-17, IL-10, IL-7, VEGF), and cluster 4 (n=37)(IL-8, IL-4, PDGF-β, IL-6, CCL11). Demographics, PAH etiologies, comorbidities, and medications were similar across clusters. Non-invasive and hemodynamic surrogates of clinical risk identified cluster 1 as high-risk and cluster 3 as low-risk groups. Five-year transplant-free survival rates were unfavorable for cluster 1 (47.6%, CI 35.4-64.1%) and favorable for cluster 3 (82.4%, CI 72.0-94.3%)(across-cluster p<0.001). Findings were replicated in the validation cohort, where machine learning classified four immune clusters with comparable proteomic, clinical, and prognostic features.Blood cytokine profiles distinguish PAH immune phenotypes with differing clinical risk that are independent of World Health Organization Group 1 subtypes. These phenotypes could inform mechanistic studies of disease pathobiology and provide a framework to examine patient responses to emerging therapies targeting immunity.

  View details for PubMedID 30661465

• Circulating plasmablasts are elevated and produce pathogenic anti-endothelial cell autoantibodies in idiopathic pulmonary arterial hypertension. European journal of immunology Blum, L. K., Cao, R. R., Sweatt, A. J., Bill, M. n., Lahey, L. J., Hsi, A. C., Lee, C. S., Kongpachith, S. n., Ju, C. H., Mao, R. n., Wong, H. H., Nicolls, M. R., Zamanian, R. T., Robinson, W. H. 2018

  Abstract

  Idiopathic pulmonary arterial hypertension (IPAH) is a devastating pulmonary vascular disease in which autoimmune and inflammatory phenomena are implicated. B cells and autoantibodies have been associated with IPAH and identified as potential therapeutic targets. However, the specific populations of B cells involved and their roles in disease pathogenesis are not clearly defined. We aimed to assess the levels of activated B cells (plasmablasts) in IPAH, and to characterize recombinant antibodies derived from these plasmablasts. Blood plasmablasts are elevated in IPAH, remain elevated over time, and produce IgA autoantibodies. Single-cell sequencing of plasmablasts in IPAH revealed repertoires of affinity-matured antibodies with small clonal expansions, consistent with an ongoing autoimmune response. Recombinant antibodies representative of these clonal lineages bound known autoantigen targets and displayed an unexpectedly high degree of polyreactivity. Representative IPAH plasmablast recombinant antibodies stimulated human umbilical vein endothelial cells to produce cytokines and overexpress the adhesion molecule ICAM-1. Together, our results demonstrate an ongoing adaptive autoimmune response involving IgA plasmablasts that produce anti-endothelial cell autoantibodies in IPAH. These antibodies stimulate endothelial cell production of cytokines and adhesion molecules, which may contribute to disease pathogenesis. These findings suggest a role for mucosally-driven autoimmunity and autoimmune injury in the pathogenesis of IPAH. This article is protected by copyright. All rights reserved.

  View details for PubMedID 29369345

• Identification of Biomarkers Predictive of Pulmonary Arterial Hypertension in Systemic Sclerosis Kolstad, K. D., Holmes, T., Rosenberg-Hasson, Y., Sweatt, A., Zamanian, R. T., Li, S., Steen, V. D., Utz, P. J., Chung, L. WILEY. 2017

  View details for Web of Science ID 000411824101041

• Right Heart End-Systolic Remodeling Index Strongly Predicts Outcomes in Pulmonary Arterial Hypertension: Comparison With Validated Models. Circulation. Cardiovascular imaging Amsallem, M., Sweatt, A. J., Aymami, M. C., Kuznetsova, T., Selej, M., Lu, H., Mercier, O., Fadel, E., Schnittger, I., McConnell, M. V., Rabinovitch, M., Zamanian, R. T., Haddad, F. 2017; 10 (6)

  Abstract

  Right ventricular (RV) end-systolic dimensions provide information on both size and function. We investigated whether an internally scaled index of end-systolic dimension is incremental to well-validated prognostic scores in pulmonary arterial hypertension.From 2005 to 2014, 228 patients with pulmonary arterial hypertension were prospectively enrolled. RV end-systolic remodeling index (RVESRI) was defined by lateral length divided by septal height. The incremental values of RV free wall longitudinal strain and RVESRI to risk scores were determined. Mean age was 49±14 years, 78% were female, 33% had connective tissue disease, 52% were in New York Heart Association class ≥III, and mean pulmonary vascular resistance was 11.2±6.4 WU. RVESRI and right atrial area were strongly connected to the other right heart metrics. Three zones of adaptation (adapted, maladapted, and severely maladapted) were identified based on the RVESRI to RV systolic pressure relationship. During a mean follow-up of 3.9±2.4 years, the primary end point of death, transplant, or admission for heart failure was reached in 88 patients. RVESRI was incremental to risk prediction scores in pulmonary arterial hypertension, including the Registry to Evaluate Early and Long-Term PAH Disease Management score, the Pulmonary Hypertension Connection equation, and the Mayo Clinic model. Using multivariable analysis, New York Heart Association class III/IV, RVESRI, and log NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) were retained (χ(2), 62.2; P<0.0001). Changes in RVESRI at 1 year (n=203) were predictive of outcome; patients initiated on prostanoid therapy showed the greatest improvement in RVESRI. Among right heart metrics, RVESRI demonstrated the best test-retest characteristics.RVESRI is a simple reproducible prognostic marker in patients with pulmonary arterial hypertension.

  View details for DOI 10.1161/CIRCIMAGING.116.005771

  View details for PubMedID 28592589

• Features and Outcomes of Methamphetamine Associated Pulmonary Arterial Hypertension. American journal of respiratory and critical care medicine Zamanian, R. T., Hedlin, H. n., Greuenwald, P. n., Wilson, D. M., Segal, J. I., Jorden, M. n., Kudelko, K. n., Liu, J. n., Hsi, A. n., Rupp, A. n., Sweatt, A. J., Tuder, R. n., Berry, G. J., Rabinovitch, M. n., Doyle, R. L., De Jesus Perez, V. n., Kawut, S. M. 2017

  Abstract

  While amphetamines are recognized as "likely" agents to cause drugs and toxins associated pulmonary arterial hypertension (PAH), (meth)amphetamine associated PAH (Meth-APAH) has not been well described.To prospectively characterize the clinical presentation, histopathology, and outcomes of Meth-APAH compared to those of idiopathic PAH (iPAH).We performed a prospective cohort study of Meth-APAH and iPAH patients presenting to the Stanford University Pulmonary Hypertension Program between 2003-2015. Clinical, pulmonary angiography, histopathology, and outcomes data were compared. We used data from the Healthcare Cost and Utilization Project to estimate the epidemiology of PAH in (meth)amphetamine abusers hospitalized in California.The study sample included 90 Meth-APAH and 97 iPAH patients. Meth-APAH patients were less likely to be female, but similar in age, body mass index, and six minute walk distance to iPAH patients. Meth-PAH patients reported more advanced heart failure symptoms, had significantly higher right atrial pressure (12.7±6.8 vs. 9.8±5.1 mmHg, p=0.001), and lower stroke volume index (22.2±7.1 vs 25.5±8.7 mL/m2, p=0.01). Event-free survival in Meth-APAH was 64.2%, 47.2%, and 25% at 2.5, 5, and 10 years respectively, representing more than double the risk of clinical worsening or death compared to iPAH (HR 2.04, 95% CI 1.28-3.25, p=0.003) independent of confounders. California data demonstrated a 2.6 fold increase in risk of PAH diagnosis in hospitalized (meth)amphetamine users.Meth-APAH is a severe and progressive form of PAH with poor outcomes. Future studies should focus on mechanisms of disease and potential therapeutic considerations.

  View details for PubMedID 28934596

• Serial Vasoreactivity Reassessment is a Prognostic Tool in Pulmonary Arterial Hypertension American Journal of Respiratory and Critical Care Medicine Sweatt, A., Spiekerkoetter, E., Hsi, A., Sung, Y., De Jesus Perez, V., Kudelko, K., Zamanian, R. 2016; 193: A6464
• DLCO Change in Pulmonary Arterial Hypertension Reflects Vascular Function as Determined by Longitudinal Response to Inhaled Nitric Oxide American Journal of Respiratory and Critical Care Medicine Sweatt, A., Spiekerkoetter, E., Hsi, A., Sung, Y., Kudelko, K., De Jesus Perez, V., Zamanian, R. 2016; 193: A7320
• Right Heart End-Systolic Remodeling Index Strongly Predicts Outcomes in Pulmonary Arterial Hypertension, Insights From a Network Analysis Circulation Amsallem, M., Sweatt, A., Aymami, M., Kuznetsova, T., Mercier, O., Fadel, E., McConnell, M., Rabinovitch, M., Zamanian, R., Haddad, F. 2016; 134: A18038
• Comprehensive Characterization of Insulin Resistance and its Association with Ventricular Function in Pulmonary Hypertension American Journal of Respiratory and Critical Care Medicine Wells, R., Sweatt, A., Cuttica, M., Dash, R., Abbasi, F., Van de Veerdonk, M., Preston, I., Hemnes, A., Gomberg-Maitland, M., Zamanian, R. 2016; 193: A6462
• Evaluation of Changes in Static and Pulsatile Hemodynamic Indices Across Longitudinal Vasoreactivity Tests in Pulmonary Arterial Hypertension American Journal of Respiratory and Critical Care Medicine Sweatt, A., Spiekerkoetter, E., Hsi, A., Sung, Y., Kudelko, K., De Jesus Perez, V., Zamanian, R. 2016; 193: A7319
• Kaposiform Lymphangiomatosis: An Unforeseen Cause of Spontaneous Hemothorax and Episodic Hemoptysis American Journal of Respiratory and Critical Care Medicine Sweatt, A., Regalia, K. 2016; 193: A3346
• Using Near-Infrared Spectroscopy to Characterize the Effects of Inhaled Nitric Oxide on Skeletal Muscle Oxygen Saturation in Adults with Pulmonary Arterial Hypertension American Journal of Respiratory and Critical Care Medicine Brian, S., Kholdani, C., Sweatt, A., Hedlin, H., Hsi, A., Spiekerkoetter, E., Zamanian, R. 2016; 193: A3961
• High Prevalence of Gastroparesis in Post-Lung Transplant Patients and Pyloric Botox for the Prevention of Bronchiolitis Obliterans Syndrome American Journal of Gastroenterology Regalia, K., Sweatt, A., Wang, L., Nguyen, L. 2015; 110: S1028
• Evolving Epidemiology and Definitions of the Acute Respiratory Distress Syndrome and Early Acute Lung Injury CLINICS IN CHEST MEDICINE Sweatt, A. J., Levitt, J. E. 2014; 35 (4): 609-?

  Abstract

  This article reviews the evolving definitions and epidemiology of the acute respiratory distress syndrome (ARDS) and highlights current efforts to improve identification of high-risk patients, thus to target prevention and early treatment before progression to ARDS. This information will be important for general practitioners and intensivists interested in improving the care of patients at risk for ARDS, and clinical researchers interested in designing clinical trials targeting the prevention and early treatment of acute lung injury.

  View details for DOI 10.1016/j.ccm.2014.08.002

  View details for Web of Science ID 000346214200002

• Interventional Pulmonologist Perspective: Treatment of Malignant Pleural Effusion CURRENT TREATMENT OPTIONS IN ONCOLOGY Sweatt, A. J., Sung, A. 2014; 15 (4): 625-643

  Abstract

  The management of known malignant pleural effusions focuses around the initial thoracentesis and subsequent objective and subjective findings. A completely reexpanded lung after fluid removal and with symptomatic improvement predicts successful pleurodesis. Pleurodesis method depends on center expertise as well as patient preference. Medical thoracoscopy does not require the operating room setting and is performed on the spontaneously breathing patient with similar success rate to surgical thoracoscopy in the appropriately selected patients. However, it is not widely available. Talc insufflation is preferred for even distribution of sprayed particles to pleural surfaces. Most often, patients can be discharged home within 24 to 48 hours after continuous chest tube suction. Indwelling pleural catheter has become popular given the ease of insertion and patient centered home drainage. Coordinated care with good patient and family education and support is paramount to maximizing the beneficial potential of the catheter. Complications are minimal, and catheters are easily removed if patients can no longer benefit from drainage, or if pleurodesis has occurred. In the setting of trapped lung as a result of visceral pleura encasement from tumor, indwelling catheter can still be useful if the patient improves with thoracentesis. However, if no subjective improvement is seen after thoracentesis for trapped lung, then no procedure is recommended and other modes of palliation should be sought.

  View details for DOI 10.1007/s11864-014-0312-6

  View details for Web of Science ID 000344532800009

• Interventional pulmonologist perspective: treatment of malignant pleural effusion. Current treatment options in oncology Sweatt, A. J., Sung, A. 2014; 15 (4): 625-643

  Abstract

  The management of known malignant pleural effusions focuses around the initial thoracentesis and subsequent objective and subjective findings. A completely reexpanded lung after fluid removal and with symptomatic improvement predicts successful pleurodesis. Pleurodesis method depends on center expertise as well as patient preference. Medical thoracoscopy does not require the operating room setting and is performed on the spontaneously breathing patient with similar success rate to surgical thoracoscopy in the appropriately selected patients. However, it is not widely available. Talc insufflation is preferred for even distribution of sprayed particles to pleural surfaces. Most often, patients can be discharged home within 24 to 48 hours after continuous chest tube suction. Indwelling pleural catheter has become popular given the ease of insertion and patient centered home drainage. Coordinated care with good patient and family education and support is paramount to maximizing the beneficial potential of the catheter. Complications are minimal, and catheters are easily removed if patients can no longer benefit from drainage, or if pleurodesis has occurred. In the setting of trapped lung as a result of visceral pleura encasement from tumor, indwelling catheter can still be useful if the patient improves with thoracentesis. However, if no subjective improvement is seen after thoracentesis for trapped lung, then no procedure is recommended and other modes of palliation should be sought.

  View details for DOI 10.1007/s11864-014-0312-6

  View details for PubMedID 25240411

• Evolving epidemiology and definitions of the acute respiratory distress syndrome and early acute lung injury. Clinics in chest medicine Sweatt, A. J., Levitt, J. E. 2014; 35 (4): 609-624

  Abstract

  This article reviews the evolving definitions and epidemiology of the acute respiratory distress syndrome (ARDS) and highlights current efforts to improve identification of high-risk patients, thus to target prevention and early treatment before progression to ARDS. This information will be important for general practitioners and intensivists interested in improving the care of patients at risk for ARDS, and clinical researchers interested in designing clinical trials targeting the prevention and early treatment of acute lung injury.

  View details for DOI 10.1016/j.ccm.2014.08.002

  View details for PubMedID 25453413

• A Microarray Biosensor for Multiplexed Detection of Microbes Using Grating-Coupled Surface Plasmon Resonance Imaging ENVIRONMENTAL SCIENCE & TECHNOLOGY Marusov, G., Sweatt, A., Pietrosimone, K., Benson, D., Geary, S. J., Silbart, L. K., Challa, S., Lagoy, J., Lawrence, D. A., Lynes, M. A. 2012; 46 (1): 348-359

  Abstract

  Grating-coupled surface plasmon resonance imaging (GCSPRI) utilizes an optical diffraction grating embossed on a gold-coated sensor chip to couple collimated incident light into surface plasmons. The angle at which this coupling occurs is sensitive to the capture of analyte at the chip surface. This approach permits the use of disposable biosensor chips that can be mass-produced at low cost and spotted in microarray format to greatly increase multiplexing capabilities. The current GCSPRI instrument has the capacity to simultaneously measure binding at over 1000 unique, discrete regions of interest (ROIs) by utilizing a compact microarray of antibodies or other specific capture molecules immobilized on the sensor chip. In this report, we describe the use of GCSPRI to directly detect multiple analytes over a large dynamic range, including soluble protein toxins, bacterial cells, and viruses, in near real-time. GCSPRI was used to detect a variety of agents that would be useful for diagnostic and environmental sensing purposes, including macromolecular antigens, a nontoxic form of Pseudomonas aeruginosa exotoxin A (ntPE), Bacillus globigii, Mycoplasma hyopneumoniae, Listeria monocytogenes, Escherichia coli, and M13 bacteriophage. These studies indicate that GCSPRI can be used to simultaneously assess the presence of toxins and pathogens, as well as quantify specific antibodies to environmental agents, in a rapid, label-free, and highly multiplexed assay requiring nanoliter amounts of capture reagents.

  View details for DOI 10.1021/es201239f

  View details for Web of Science ID 000298762900047

  View details for PubMedID 22029256

• The effect of plasma transfusion on oxygenation in critically ill patients with chronic liver disease American Journal of Respiratory and Critical Care Medicine Sweatt, A., Biggins, S., Rosen, H., Clark, B., Smart, A., Moss, M., Benson, A. 2012; 185: A1151
• A Case of Multi-Organ Langerhans Cell Histiocytosis Responsive to Tobacco Cessation American Journal of Respiratory and Critical Care Medicine Sweatt, A., Rizeq, M., Sandberg, M. 2012; 185: A5429
• A dosing formula for INR-targeted plasma transfusion in bleeding patients with chronic liver disease American Journal of Respiratory and Critical Care Medicine Sweatt, A., Moss, M., Tripputi, M., Benson, A. 2011; 183: A5828
• Spastic Esophageal Motility Disorders in Post-Lung Transplant Patients 59th Annual Aspen Lung Conference Regalia, K., Sweatt, A., Chhatwani, L., Mooney, J., Dhillon, G., Nguyen, L. 2016
• When a Pain in the Neck May Have Helped: Painless Subacute Granulomatous Thyroiditis Causing Fever of Unknown Origin American College of Physicians National Meeting Sweatt, A., Mascolo, M. 2012